Abstract
Human plasma chitotriosidase activity is a commonly used diagnostic and therapeutic biomarker for non-neuronopathic Gaucher disease. Chitotriosidase deficiency is common in non-African populations and is primarily caused by a 24 bp duplication in the encoding gene (CHIT1). Allele frequencies for the 24 bp duplication range from 20–50 % outside Africa. The present study found chitotriosidase deficiency to be rare in the South African Black population (1.6 %) and the otherwise common 24 bp duplication is absent in this African population. Instead, chitotriosidase deficiency is caused by a 4 bp deletion across the exon/intron 10 boundary (E/I-10_delGAgt) of the CHIT1 gene. The exact position of this mutation was found to differ from the previously reported location. Allele frequencies for six coding variants of CHIT1 (p.G102S, p.G354R, 24 bp duplication, E/I-10_delGAgt, p.A442V/G) were determined and the 4 bp deletion was found to be in complete linkage disequilibrium (LD) with two of the coding variants (p.G354R and p.A442V). The in silico assessments of the two missense mutations in LD predict a protein-damaging nature and functional studies are needed to clarify if one or both abolish the enzyme’s activity. Overall, the low frequency of chitotriosidase deficiency in South African Blacks makes chitotriosidase activity an excellent biomarker of choice in this population.
Competing interests: None declared
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Acknowledgements
This study was supported by the South African National Health Laboratory Service Research Trust. We would like to thank Jennifer Kromberg from the Mellon Research Foundation at the University of the Witwatersrand, and M. Ramsay and A. Nebel for useful comments on the manuscript.
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Communicated by: Verena Peters
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Arndt, S., Hobbs, A., Sinclaire, I., Lane, A.B. (2012). Chitotriosidase Deficiency: A Mutation Update in an African Population. In: Zschocke, J., Gibson, K., Brown, G., Morava, E., Peters, V. (eds) JIMD Reports - Volume 10. JIMD Reports, vol 10. Springer, Berlin, Heidelberg. https://doi.org/10.1007/8904_2012_193
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DOI: https://doi.org/10.1007/8904_2012_193
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